A Study of AT2101 (Afegostat Tartrate) in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy

A Randomized, Open-label Study to Assess the Safety and Tolerability of Multiple Dose Levels and Multiple Dosing Regimens of AT2101 in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy

This study was conducted to test the safety and tolerability of afegostat tartrate in participants with type 1 Gaucher disease already receiving enzyme replacement therapy.

This was a Phase 2, open-label study in participants with Gaucher disease, a lysosomal storage disorder. Afegostat tartrate (also known as AT2101 or isofagomine tartrate) is designed to act as a pharmacological chaperone by selectively binding to misfolded β-glucocerebrosidase (GCase) and helping it fold correctly, intended to restore GCase activity. The study consisted of a 14-day screening period, a 28-day treatment period, and a 7-day wash-out period. Participants received 1 of 4 dosing regimens for afegostat tartrate.

Inclusion Criteria:

• Had a confirmed diagnosis of type 1 Gaucher disease with a known documented missense gene mutation in at least 1 of the 2 gene-encoding β-glucosidase alleles
• Clinically stable
• Male or female participants, 18 to 74 years old inclusive
• All participants of childbearing potential used adequate birth control
• Provided written informed consent to participate in the study

Exclusion Criteria:

• Clinically significant disease, severe complications from Gaucher disease, or serious illness that precluded participation in the study in the opinion of the Investigator that compromised the safety of the participant or precluded the participant from completing the study
• During the screening period, any clinically significant findings, as deemed by the Investigator
• Partial or total splenectomy (removal of spleen) within the 2 years prior to study entry
• History of pulmonary hypertension or Gaucher related lung disease
• History of allergy or sensitivity to the study drug or any excipients, including any prior serious adverse reaction to iminosugars (for example, N-butyldeoxynojirimycin or miglustat)
• Pregnant or breast-feeding
• Current/recent drug or alcohol abuse
• Treatment with any investigational product in the 90 days before study entry
• Treatment in the previous 90 days with any drug known to have a well-defined potential for toxicity to a major organ
• Presence or symptoms of gastrointestinal, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs